This proposal describes a linkage study of autosomal dominant glaucoma (ADG). The purpose of this study is to establish the chromosomal location of the gene responsible for this condition. To facilitate this study, the applicant has identified twenty pedigrees from the New England area affected with a type of juvenile onset glaucoma that exhibits autosomal dominant inheritance. One family (ADG-4), has been traced through six generations. Affected individuals in all families develop high pressure glaucoma by twenty years of age and all but two have required surgery for treatment. Gonioscopic analysis of these patients shows normal angle structures without excessive pigmentation or an increased number of iris processes. For linkage studies, genetic markers will be selected at intervals of 10-15 centimorgans throughout the genome. Linkage calculations will be performed with assistance from Dr. Jonathan Haines using a VAX 4500 computer. Preliminary linkage analysis has been performed using selected marker loci which have been shown to be linked to the disease trait in some families affected with the Stickler's syndrome and the Rieger's syndrome. These syndromes are inherited as autosomal dominant traits and are associated with a juvenile onset open angle glaucoma. These preliminary data suggest that pedigree ADG-4 is not linked to these markers and that ADG is not related to these syndromes. Demonstrating linkage between ADG and a genetic marker will allow new methods of molecular diagnosis to be developed. Although not a part of this application, this study is a first step toward the cloning of a gene responsible for hereditary glaucoma. Characterization of the gene and protein product that can result in ADG will provide valuable new insights into the pathogenesis of this condition as well as have an enormous impact on the clinical diagnosis and treatment of affected individuals.